Other Talks in the Category: Diseases, Disorders & Treatments

Hello, my name is Paul Kim, and I'm an assistant professor at McMaster University in Canada. This seminar will focus on the "Advances in Fibrinolysis", mostly discussing the basic science aspects of fibrinolysis research. I will also discuss clinical application of these findings and thrombolytic therapy.
Coagulation and fibrinolysis exist as a fine hemostatic balance. The left side represents the coagulation cascade, which is shown by the conversion of prothrombin to thrombin. Thrombin, the central enzyme in coagulation cleaves soluble fibrinogen into insoluble fibrin clot. The right-hand side represents the fibrinolytic cascade, which is shown by the conversion of plasminogen to plasmin. Plasmin, the essential enzyme in fibrinolysis digests insoluble fiber in clots to soluble fibrin degradation products, or FDPs.
The loss of this balance leads to various pathological outcomes; uncontrolled up regulation of the coagulation cascade leads to thrombotic diseases such as deep vein thrombosis, heart attacks, and ischemic strokes.
Alternatively, uncontrolled up regulation of the fibrinolytic cascade leads to bleeding episodes or hemorrhaging.
Therefore, the positive feedback systems inherent to both the coagulation and fibrinolytic systems are regulated by inhibitory mechanisms. Thrombin generation is down-regulated by the activation of protein C to form activated protein C. Plasmin generation is down-regulated by the activation of thrombin activatable fibrinolysis inhibitor, or TAFI, to generate TAFI a. Central to activation of protein C and TAFI is the thrombin thrombomodulin complex. Thrombomodulin, a trans-membrane protein expressed on the surface of endothelial cells, bind with thrombin, which then act to alter the substrate specificity of thrombin from a pro-coagulant state to an anti-coagulant state.